title: Clinical applications of cell-based approaches in alveolar bone augmentation: a systematic review.
abstract: BACKGROUND
  Cell-based approaches, utilizing adult mesenchymal stem cells (MSCs), are reported to overcome the limitations of conventional bone augmentation procedures.
  
  
  OBJECTIVE
  The study aims to systematically review the available evidence on the characteristics and clinical effectiveness of cell-based ridge augmentation, socket preservation, and sinus-floor augmentation, compared to current evidence-based methods in human adult patients.
  
  
  METHODS
  MEDLINE, EMBASE, and CENTRAL databases were searched for related literature. Both observational and experimental studies reporting outcomes of "tissue engineered" or "cell-based" augmentation in ≥5 adult patients alone, or in comparison with non-cell-based (conventional) augmentation methods, were eligible for inclusion. Primary outcome was histomorphometric analysis of new bone formation. Effectiveness of cell-based augmentation was evaluated based on outcomes of controlled studies.
  
  
  RESULTS
  Twenty-seven eligible studies were identified. Of these, 15 included a control group (8 randomized controlled trials [RCTs]), and were judged to be at a moderate-to-high risk of bias. Most studies reported the combined use of cultured autologous MSCs with an osteoconductive bone substitute (BS) scaffold. Iliac bone marrow and mandibular periosteum were frequently reported sources of MSCs. In vitro culture of MSCs took between 12 days and 1.5 months. A range of autogenous, allogeneic, xenogeneic, and alloplastic scaffolds was identified. Bovine bone mineral scaffold was frequently reported with favorable outcomes, while polylactic-polyglycolic acid copolymer (PLGA) scaffold resulted in graft failure in three studies. The combination of MSCs and BS resulted in outcomes similar to autogenous bone (AB) and BS. Three RCTs and one controlled trial reported significantly greater bone formation in cell-based than conventionally grafted sites after 3 to 8 months.
  
  
  CONCLUSIONS
  Based on limited controlled evidence at a moderate-to-high risk of bias, cell-based approaches are comparable, if not superior, to current evidence-based bone grafting methods, with a significant advantage of avoiding AB harvesting. Future clinical trials should additionally evaluate patient-based outcomes and the time-/cost-effectiveness of these approaches.
authors.affiliation: Private practice, Mumbai, India.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Shanbhag
authors.forename: Vivek
authors.initials: V
authors.lastname: Shanbhag
mesh_terms: D000540:Alveolar Ridge Augmentation / Q000379:methods*; D018786:Bone Substitutes; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059546:Sinus Floor Augmentation / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D018786:Bone Substitutes
keywords: bone augmentation; bone grafting; stem cells